The aim of this study was to compare the efficacy and safety of adding manidipine 20 mg versus amlodipine 10 mg to the treatment of diabetic patients with uncontrolled hypertension and microalbuminuria despite full-dose treatment with a renin-angiotensin system blocker for at least 6 months. Patients were randomized to receive manidipine (n = 61) or amlodipine (n = 30) in a 2:1 ratio for 6 months and monitored for microalbuminuria for an additional extension phase of 18 months. Manidipine and amlodipine decreased blood pressure values to a similar extent. Urinary albumin excretion was reduced by 65.5% with manidipine versus 20% with amlodipine (p < 0.01) at 6 months and 62.7 versus 16.6% (p < 0.01) at the end of the extension phase. Manidipine was better tolerated than amlodipine. Thus, the addition of manidipine, but not amlodipine, resulted in a large reduction in the urinary albumin excretion rate despite similar blood pressure reductions.